Background: Alprazolam, a newer benzodiazepine, may be useful in the control of nausea and vomiting in breast cancer patients. Methods: Nineteen operable breast cancer patients were included in this randomized prospective crossover open-label trial. Patients received either granisetron (G) alone, or in combination with alprazolam (A). Group A patients received G+A first and then crossed over to G-alone after the 2nd or 3rd cycle. Group B patients received the reverse order. Eighty-four cycles were evaluated. Results: In group A, complete remission (CR) plus major response (MR) was higher (93.9%) with G+A than with G-alone (83.3%; p = 0.0001) in the first 24-hour period. In group B, CR plus MR was higher in G+A cycles (100%) than in G-alone cycles (85.7%; p = 0.035) in the 24-hour period and in the 25- to 129-hour period (92 vs. 90.5%, respectively; p = 0.022). Conclusion: Alprazolam increases the efficacy of granisetron in patients with breast cancer treated with an anthracycline-containing regimen. Copyright (C) 2005 S. Karger AG, Basel.